On Thu, Oct 14, 2010, Lars Skjærven wrote:
> I'm attempting to measure the binding free-energy of a protein-protein
> complex. Ligand binding to each of the two protein subunits are assumed to
> weaken the binding energy between them.
>
> Thus, I performed 6 MD simulations of the complex with the two ligands, and
> 6 MD simulations without the ligands. All simulations are 50 ns long. MMPBSA
> was then used on each of the simulations to measure the binding free energy
> in the two cases. 500 frames from each of the simulations were used in the
> MMPBSA calculation.
All your results seem quite reasonable. What is called "protein" and "ligand"
is arbitrary, and your identification seems fine. It's also very good to run
multiple simulations. What you are seeing looks to me like "natural"
fluctuations in estimates of protein-protein binding energies, although the
values are all very negative....are you leaving out the entropy contributions?
The "case 2" numbers do have bigger fluctuations: you could look for
structural differences in the individual simulations that might explain some
of this. A good thing to do would be to pool all the snapshots (say for "case
2"), then cluster them. If important clusters have structures from each of
the six simulations, that would be good. If not, you would have evidence that
individual simulations were getting trapped in some region of configuration
space.
Using MMPBSA for protein-protein interactions is a challenge; if you haven't
done so, please check out this paper:
%A H. Gohlke
%A D.A. Case
%T Converging Free Energy Estimates: MM-PB(GB)SA Studies on the
Protein-Protein Complex Ras-Raf
%J J. Comput. Chem.
%V 25
%P 238-250
%D 2004
....good luck....dac
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Received on Thu Oct 14 2010 - 06:30:05 PDT
